Short communication

Diabetologia

, Volume 42, Issue 3, pp 358-364

Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients

  • F. AndreelliAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France
  • , M. LavilleAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France
  • , P.-H. DucluzeauAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France
  • , N. VegaAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France
  • , P. VallierAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France
  • , Y. KhalfallahAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France
  • , J.-P. RiouAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France
  • , H. VidalAffiliated withINSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, France

Summary

We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85α-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. The in vivo regulation by insulin was studied using a 3-h euglycaemic, hyperinsulinaemic clamp. There were no differences in the basal concentrations of the three mRNAs in skeletal muscle between groups. Insulin infusion produced a twofold reduction in insulin receptor substrate-1 mRNA expression in the three groups (p < 0.02). In contrast, insulin increased p85α-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects ( + 98 ± 22 % in lean and + 127 ± 16 % in obese, p < 0.02) but this effect was totally impaired in Type II diabetic patients ( + 5 ± 12 %, NS). A similar defect in insulin action on p85α-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue ( + 138 ± 25 %, p < 0.01 in lean and + 46 ± 14 %, p < 0.02 in obese and + 29 ± 11 %, NS in Type II diabetic patients). The lack of action of insulin on p85α-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. [Diabetologia (1999) 42: 358–364]

Keywords Hyperinsulinaemic clamp insulin receptor IRS-1 RT-PCR.